A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of Orally Administered Lumicitabine (JNJ-64041575) Regimens in Hospitalized Infants and Children Aged 28 Days to 36 Months Infected With Respiratory Syncytial Virus
Overview
- Phase
- Phase 2
- Intervention
- Lumicitabine
- Conditions
- Respiratory Syncytial Viruses
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 7
- Locations
- 29
- Primary Endpoint
- Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to determine in hospitalized infants and children who are infected with respiratory syncytial virus (RSV) the dose-response relationship of multiple regimens of lumicitabine on antiviral activity based on nasal RSV shedding using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR).
Detailed Description
RSV is a leading cause of lower respiratory tract disease in infants. Most infants and children who get RSV recover fully after 1-2 weeks, but RSV infection can sometimes worsen and may lead to hospitalization and admission into an intensive care unit. The main purpose of this study is to learn how well the study drug (lumicitabine, also known as JNJ-64041575 or ALS-008176) works, how the human body handles the study drug, which dose of the study drug is effective for treatment of RSV infection in infants/children and how safe it is compared to a placebo (placebo looks just like lumicitabine \[given in same way\] but has no effect against RSV). Approximately up to 180 participants aged between 28 days to 36 months and hospitalized with RSV infection will take part in this world-wide study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants hospitalized (or in emergency room \[ER\]) at the time of randomization and unlikely to be discharged for the first 24 hours after randomization
- •Participants diagnosed with respiratory syncytial virus (RSV) infection using a polymerase chain reaction (PCR)-based molecular diagnostic assay, with or without co-infection with another respiratory pathogen (respiratory virus or bacteria)
- •Participants who have an acute respiratory illness with signs and symptoms consistent with a viral infection (for example, fever, cough, nasal congestion, runny nose, sore throat, myalgia, lethargy, shortness of breath, or wheezing) with onset less than or equal to \<=5 days from the anticipated time of randomization. Onset of symptoms is defined as the first time (within 1 hour) the parent(s)/caregiver(s) becomes aware of respiratory or systemic symptoms of RSV infection
- •With the exception of the symptoms related to the RSV infection or defined comorbid condition for severe RSV disease (prematurity at birth \[participant's gestational age was less than {\<}37 weeks; for infants \<1 year old at randomization\], bronchopulmonary dysplasia, congenital heart disease, other congenital diseases, Down syndrome, neuromuscular impairment, or cystic fibrosis), participant must be medically stable on the basis of physical examination, medical history, vital signs/peripheral capillary oxygen saturation (SpO2), and electrocardiogram (ECG) performed at screening. If there are abnormalities, they must be consistent with the underlying condition in the study population and/or the RSV infection. This determination must be recorded in the participant's source documents and initialed by the investigator. Participants with comorbidities will be allowed to be enrolled once the Independent Data Monitoring Committee (IDMC) has reviewed the pharmacokinetic (PK) and safety data of the highest dose that will be used in this study and once the IDMC has recommended opening recruitment to this group. Sites will be notified when the restriction is lifted
- •The participant's estimated glomerular filtration rate (eGFR) is not below the lower limit of normal for the participant's age
Exclusion Criteria
- •Participants who are not expected to survive for more than 48 hours
- •Participants who have had major thoracic or abdominal surgery in the 6 weeks prior to randomization
- •Participants who have a known or suspected immunodeficiency (except immunoglobulin A \[IgA\] deficiency), such as a known human immunodeficiency virus infection
- •Participants being treated with extracorporeal membrane oxygenation
- •Participant receiving chronic oxygen therapy at home prior to admission
- •Participants who have a poorly functioning gastrointestinal tract (that is, unable to absorb drugs or nutrition via enteral route)
Arms & Interventions
Regimen A (Low-Dose Lumicitabine)
Participants will receive a single 40 milligram per kilogram (mg/kg) loading dose (LD) (Dose 1) followed by nine 20 mg/kg maintenance doses (MDs) (Doses 2 to 10) of lumicitabine twice daily up to Day 5/6.
Intervention: Lumicitabine
Regimen B (High-Dose Lumicitabine)
Participants will receive a single 60 mg/kg LD (Dose 1) followed by nine 40 mg/kg MDs (Doses 2 to 10) of lumicitabine twice daily up to Day 5/6.
Intervention: Lumicitabine
Regimen C (Placebo)
Participants will receive either a single 40 mg/kg placebo LD (Dose 1) followed by nine 20 mg/kg maintenance dose (MDs) (Doses 2 to 10) of placebo twice daily or single 60 mg/kg placebo LD (Dose 1) followed by nine 40 mg/kg placebo MDs (Doses 2 to 10), twice daily up to Day 5/6.
Intervention: Placebo
Outcomes
Primary Outcomes
Area Under the Curve (AUC) of Respiratory Syncytial Virus (RSV) Viral Load
Time Frame: Day 1 to 7: Predose, 0.25 and 2 hours postdose
AUC of RSV viral load was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay of the mid-turbinate nasal swab.
Secondary Outcomes
- Number of Participants With Electrocardiogram (ECG) Abnormalities(Up to 28 days)
- Area Under Plasma Concentration-time Curve (AUC) of JNJ-63549109 (Metabolite of Lumicitabine)(Day 1 and Day 5)
- Trough Observed Analyte Concentration (C[Trough]) of JNJ-63549109 (Metabolite of Lumicitabine)(Day 1 and Day 5)
- Predicted Concentration of JNJ-63549109 (Metabolite of Lumicitabine) at 12 Hours Postdose (C12h)(12 hours postdose)
- Duration of ICU Stay(Up to 28 days)
- Number of Participants Who Required Invasive Mechanical Ventilation Support(Up to 28 days)
- Time From Initiation of Study Treatment Until Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to (>=)93 Percent (%) on Room Air Among Participants Who Were Not on Supplemental Oxygen Prior to Onset of Respiratory Symptoms(Up to 28 days)
- Time for SpO2 to Return to Pre-RSV Infection Status(Up to 28 days)
- Peak Viral Load(Up to 28 days)
- Time for Respiratory Rate to Return to Pre-RSV Infection Status(Up to 28 days)
- Number of Participants With Emergent Adverse Event(Up to 28 days)
- Number of Participants Admitted to the Intensive Care Unit (ICU)(Up to 28 days)
- Number of Participants Who Required Non-invasive Mechanical Ventilation Support(Up to 28 days)
- Duration of Supplemental Oxygen(Up to 28 days)
- Time to no Longer Requiring Supplemental Oxygen(Up to 28 days)
- Number of Participants With Clinically Significant Physical Examinations Abnormalities(Up to 28 days)
- Duration of Invasive Mechanical Ventilation Support(Up to 28 days)
- Number of Participants With Emergent Clinical Relevant Vital Signs Abnormalities(Up to 28 days)
- Maximum Observed Plasma Concentration (Cmax) of JNJ-63549109 (Metabolite of Lumicitabine)(Day 1 and Day 5)
- Length of Hospital Stay(Up to 28 days)
- Number of Participants With Worst Emergent Laboratory Abnormalities (Division of Microbiology and Infectious Diseases [DMID] Toxicity Grades)(Up to 28 days)
- Number of Participants Who Required Supplemental Oxygen(Up to 28 days)
- Duration of Non-invasive Mechanical Ventilation Support(Up to 28 days)
- Number of Participants With Acute Otitis Media(Up to 28 days)
- Duration of Signs and Symptoms of RSV Infection(Up to 28 days)
- RSV Viral Load Over Time(On Day 2, 3, 4, 5, 6, 7, 10, 14 and 28)
- Time to Clinical Stability(Up to 28 days)
- Time for Body Temperature to Return To Pre-RSV Infection Status(Up to 28 days)
- AUC of RSV RNA Viral Load From Baseline up to Day 14(Baseline up to Day 14)
- Acceptability and Palatability of Lumicitabine Formulation as Assessed by Clinician Electronic Clinical Outcome Assessment (eCOA)(Up to Day 6)
- Time To Peak Viral Load(Up to 28 days)
- Severity of Signs and Symptoms of RSV Infection Assessed by the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS)(Up to 28 days)
- Percentage of Participants With Decline of Viral Load(Up to 28 days)
- Percentage of Participants With Undetectable RSV Viral Load(Up to 28 days)
- AUC of RSV RNA Viral Load From Baseline up to Day 10(Baseline up to Day 10)
- AUC of RSV Viral Load From Baseline Until 1 Day After the Last Dose of Study Drug(Baseline Until 1 Day after the last dose of study drug (up to 10 days))
- Number of Participants With Emergent Postbaseline Changes in the RSV Polymerase L-gene and Other Regions of the RSV Genome Compared With Baseline Sequences(Baseline up to 28 days)
- Time to RSV Ribonucleic Acid (RNA) Being Undetectable(Up to 28 days)